AB0351 IMPACT OF FCGR2A, FCGR3A AND FCGR3B POLYMORPHISM ON RITUXIMAB EFFICACY IN RHEUMATOID ARTHRITIS
Authors: M. Moalla, I. Mahmoud, A. Ben Tekaya, L. Rouached, S. Bouden, R. Tekaya, Y. Gorgi, L. Abdelmoula, O. Saidane, I. Sfar
Journal: Annals of the Rheumatic Diseases (2022)

Background Identifying reliable biomarkers of response to biologics in rheumatoid arthritis (RA) is necessary to improve responsiveness, preserve functions and structure of joints, as well as to reduce treatment’s cost. Single nucleotide polymorphisms (SNP’s) of Fc-gamma receptors genes (FCGRs), by inducing a variation of receptors’ affinity to Fc fragment of Gamma immunoglobulin, might influence the efficacy of therapeutic monoclonal antibodies by modifying their clearance. Objectives The aim of this study was to investigate whether FCGR2A, FCGR3A and FCGR3B SNP’s were predictive factors of response to rituximab (RTX) in Tunisian RA patients. Methods A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of patients suffering from RA treated with RTX. Treatment outcome was evaluated after 6 months, using DAS 28 variation from baseline and EULAR response criteria. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were studied using PCR-SSP and direct sequencing process. Results Thirty-four patients were enrolled with a sexe ratio M/F=5/29. The mean age at inclusion was 54,24±11,78 years [29-77]. All patients received at least one cs-DMARDS priorly to the prescription of RTX. Concomitant treatment with methotrexate was pursued in 77,3% of patients. As shown in Table 1, an association, that tend to signification, was found between R/R FCGR2A receptors and a greater variation in DAS28 score (p=0,053). This association was also found using EULAR criteria, since all patients with R/R genotypes had a good or moderate response to RTX but was not significative (p=0,131). Table 1. Correlation of FCGR SNPs with response to rituximab at 6 months of treatment Genetic study ΔDAS 28 CRP p ΔDAS 28ESR p EULAR (R-) (n=7) EULAR (R+) (n=27) P FCGR2A R131H* 0,138 0,761 0,301 Genotypes RR 2,53 ± 1,56 0,053 1,83±0,75 0,480 0(0) 7 (100) 0,131 HH 2,05±2,51 0,868 2,29±1,64 0,683 1 (33,3) 2 (66,7) 0,576 RH 1,09±1,36 0,06 2,00±1,73 0,855 6 (25) 18(75) 0,324 Alleles R 1,45±1,52 0,868 1,96±1,49 0,683 6 (0,194) 25(0,806) 0,576 H 1,17 ± 1,43 0,053 2,1±1,60 0,480 7 (0,259) 20(0,741) 0,131 FCGR3A F158V* 0,428 0,873 0,370 Genotypes FF 1,35±1,57 0,860 1,91±1,86 0,705 2 (16,7) 10(83,3) 0,676 VV 0,95±0,98 0,288 2,85±0,32 0,637 1 (10) 9(90) 0,324 FV 2,06±1,83 0,237 1,84±1,51 1 4 (33,3) 8(66,7) 0,175 Alleles F 1,72±1,70 0,288 1,87±1,56 0,637 6 (0,25) 18(0,75) 0,324 V 1,56±1,57 0,860 2,13±1,33 0,705 5(0,227) 17(0,773) 0,676 FCGR3B NA1/NA2* 0,217 0,485 0,645 Genotypes NA1NA1 2,29±1,81 0,09 2,13±1,08 0,715 2(22,2) 7 (78,8) 0,888 NA2NA2 0,79±1,30 0,329 0,6 0,343 2 (33,3) 4 (66,7) 0,395 NA1NA2 1,23±1,36 0,391 2,28±2,07 0,345 3 (15,8) 16(84,2) 0,436 Alleles NA2 1,15±1,33 0,09 1,95±1,95 0,715 5 (0,20) 20(0,80) 0,888 NA1 1,60±1,58 0,329 2,19±1,45 0,343 5 (0,179) 23(0,821) 0,395 DAS : disease activity score, ΔDAS : mean variation of DAS at 6 months , * :Comparison of the global distribution of the 3 genotypes, ** : p while comparing the prevalence of R/R genotype to R/H and H/H genotypes, R+ : good or moderate EULAR response, R - : bad EULAR response Conclusion The low affinity receptor R/R FcgRIIa might be predictive of good response in RA patients treated with RTX. More studies need to be conducted in larger cohorts to confirm this association, with the aim of identifying reliable biomarkers of response to biologics to improve responsiveness, preserve joints functions and structure, as well as reduce treatment’s cost. Disclosure of Interests None declared